Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous injection of a sublethal dose of lead acetate into a domestic pig resulted in a 4.5-fold increase of guanine in the urine, indicating an impairment in the conversion of guanine to xanthine. This impairment is probably due to the inhibition of guanine aminohydrolase (guanase), since the activity of this enzyme is inhibited by Pb2+ (the inhibition constant being 3.0 X 10(-6)M). Postmortem histological examination revealed concretions of crystalline material in the epiphyseal plate of the femoral head. Extraction of the section containing the concretions showed that they were guanine. The relation of these findings to saturnine gout is discussed.
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PMID:Saturnine gout: lead-induced formation of guanine crystals. 62 68

Representatives of the major classes of nonsteroidal antiinflammatory drugs (NSAID) were assessed for their effects on superoxide anion (O2-.) production by human polymorphonuclear leukocytes stimulated with phorbol myristate acetate or N-formyl methionyl-leucyl phenylalanine (fMLP). Three levels of effects were studied: (1) overall inhibition of O2-. production, (2) the inhibition of interaction between fMLP and specific receptors at the cell surface, and (3) intermediate proenzyme and enzyme effects. Some, but not all drugs inhibited O2-. production. In general, drugs that inhibited O2-. production inhibited fMLP-receptor interactions in a consistent dose dependent fashion, showing noncompetitive kinetics. Drugs that failed to inhibit O2-. production showed weak and variable effects on receptor binding and on the intermediate enzymes. Clinical observations suggest that inflammation in diseases such as gout respond differently to NSAID than diseases such as rheumatoid arthritis; studies of drug effects may help to clarify the differences in pathogenesis of these inflammatory diseases.
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PMID:Some nonsteroidal antiinflammatory drugs inhibit the generation of superoxide anions by activated polymorphs by blocking ligand-receptor interactions. 299 48

Numerous trials have shown the efficacy of ACE-inhibitors in moderate and severe essential hypertension. Their use must be regarded as very promising. They lower peripheral vascular resistance without influencing cardiac index and heart rate. Additionally, they maintain serum potassium and do not effect plasma lipids or provoke diabetes mellitus or gout. In 20-30% of hypertensive patients ACE-inhibitors have to be combined with diuretics and/or calcium antagonists. The addition of beta-blockers is useful in patients with resting tachycardia. In mild hypertension the use of ACE-inhibitors as first-line drugs is indicated in patients with adverse reactions to beta-blockers or diuretics. In bilateral renovascular hypertension, ACE-inhibitors may induce a strong blood pressure fall; in bilateral stenosis they contribute to a deterioration of renal function with reversible renal insufficiency. In renoparenchymal hypertension, ACE-inhibitors may attenuate the progression of renal insufficiency; in addition, proteinuria is lowered. In systolic hypertension in the elderly, one must be aware of a marked first-dose hypotensive effect. ACE-inhibitors decrease exaggerated exercise-induced elevation of blood pressure and heart rate and therefore lower myocardial oxygen consumption. In patients with hypertension and diabetes mellitus, antihypertensive treatment should be initiated for blood pressure levels above 140/90 mmHg, to attenuate the progression of vascular damage in the kidney. In patients with severe left ventricular hypertrophy, ACE-inhibitors reduce left ventricular mass within three months by about 30%. In hypertension and coronary heart disease, recent studies report benefits of ACE-inhibitors on coronary circulation. Presently available ACE-inhibitors and those in preparation do not differ in pharmacodynamic, but in pharmacokinetic properties, concerning the beginning and duration of blood pressure lowering. A hypotensive first-dose effect can be observed in diuretic pretreated patients, in severe (malignant) and renovascular hypertension. ACE-inhibitors should not be used during pregnancy or in patients with autoimmune diseases or those undergoing treatment with immunosuppressive drugs, due to the side effects of neutropenia and proteinuria, which are more often seen under these conditions. Results from long-term studies on the influence of ACE-inhibitor treatment on cardiovascular risk in mild hypertension have not been available until now. In the decision to treat mild hypertension with ACE-inhibitors as first-line drug therapy, the costs of therapy in comparison to cheaper antihypertensives must be taken into account.
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PMID:[The value of angiotensin-converting enzyme inhibitors in the treatment of hypertension]. 306 60

Indices of past lead absorption were measured and compared in patients with chronic renal failure from many causes, including some with chronic lead nephropathy. X-ray fluorescence (XRF) yielded finger bone lead concentrations by a new in vivo method. These correlated significantly with excess urinary lead following calcium di-sodium EDTA (ethylenediamine tetra-acetate) and erythrocyte lead concentration. Discriminant function analysis demonstrated that the patients in the study could be separated into two groups without any reference to the EDTA lead excretion test using the following variables, all of which contributed significantly to the discrimination. In order of importance, these were: a childhood history of acute lead poisoning, a history of gout, a family history of gout and detectable XRF finger bone lead. Although the XRF finger bone lead measurement is convenient and non-invasive, its lack of sensitivity (48%) limits its usefulness as a screening test for chronic lead nephropathy.
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PMID:Chronic lead nephropathy in Queensland: alternative methods of diagnosis. 308 47

Among affected members of a family (B. family) with excessive purine production and gout, activity of phosphoribosylpyrophosphate synthetase (EC 2.7.6.1) is 2.5- to 3.0-fold higher than among normal people. The molecular basis for this increased enzyme activity was studied. Antibody to purified human phosphoribosylpyrophosphate synthetase of erythrocytes was obtained from immunized rabbits. Studies with the IgG fraction of this antiserum show the presence of normal quantities of immunoreactive enzyme, but 2.5- to 3.0-fold higher activity per molecule in affected members of the B. family. In addition, by use of a stain for phosphoribosylpyrophosphate synthetase activity, a difference in electrophoretic mobility was demonstrated on cellulose acetate gel between the partially purified enzyme from normal people and an affected member of the B. family. These studies suggest that the enzyme aberration responsible for purine overproduction and gout in the B. family results from a structurally altered enzyme with increased activity per molecule.
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PMID:Human phosphoribosylpyrophosphate synthetase: increased enzyme specific activity in a family with gout and excessive purine synthesis. 420 Jul 23

The changes in adenine nucleotide concentration induced by acetate were investigated in rat liver in situ and in isolated rat hepatocytes. Adenosine monophosphate (AMP) concentration increased approximately threefold within 15 minutes after intraperitoneal injection of sodium acetate. A small but significant decrease in adenosine triphosphate (ATP) concentration also occurred. Consequently, the ATP/AMP ratio decreased from approximately 14 (the value found in control or sodium chloride-injected rats) to approximately 3 (the value found in sodium acetate-injected rats). Adenosine diphosphate (ADP) concentration increased slightly, but this was statistically nonsignificant. Total adenine nucleotide concentrations after acetate injection remained essentially the same as those in control rats. Adenylate energy charge decreased after acetate administration. No significant changes in nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) concentrations were found after sodium acetate injection. Similar patterns of changes in adenine nucleotide concentrations were found in isolated rat hepatocytes incubated in the presence of acetate. These data indicate that acetate, which appears in human blood either during hemodialysis with acetate-containing solution or after ethanol consumption, may alter energy equilibrium of adenine nucleotides in the liver. This is due to the conversion of ATP to AMP in the course of acetate to acetyl-coenzyme A (CoA) activation. It is therefore possible that accelerated ATP turnover in the liver may contribute both to the "intolerance to acetate" in patients subjected to dialysis with the sodium acetate-containing solution and to the pathogenesis of gout associated with excessive ethanol consumption.
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PMID:Acetate-induced changes of adenine nucleotide levels in rat liver. 849 21

Diuretics were used in most of the major trials that demonstrated that lowering the blood pressure reduced cardiovascular morbidity and mortality. Nevertheless in the second half of the eighties, there were misgivings about the widespread use of thiazide diuretics, driven in part by the relative failure of the large trials to reduce myocardial infarction-to the extent predicted by large scale epidemiological studies. There was much attention on metabolic side effects of thiazide diuretics including dyslipidaemia, glucose intolerance, hypokalaemia, hyperuricaemia, and then microalbuminuria particularly in diabetic subjects. These issues were current when JNC (IV) (1988) and the WHO-ISH guidelines (1989) were being written. Three major clinical trials SHEP, STOP and MRC published in the early nineties established that thiazide diuretics alone, or in combination with beta blockers, did reduce cardiovascular morbidity and mortality in elderly subjects with hypertension. All guidelines published since 1993 include diuretics among the first line drugs. Possibly the most important factor in the restoration of diuretics has been the use of progressively lower doses that minimise the metabolic side effects. Diuretics are effective as monotherapy in the treatment of mild essential hypertension and of isolated systolic hypertension in elderly subjects. They are very useful in combination with beta blockers or with ACE inhibitors. They should be avoided in patients with gout and should not be used as first line drugs in patients with diabetes. They should only be used with caution in young obese subjects with dyslipidaemia and increased risk of coronary artery disease, facing many decades of treatment for hypertension. However there is no doubt that diuretics are effective, cheap and have a central role in the control of hypertension in all communities around the world.
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PMID:[Role of diuretics in the treatment of hypertension: from large controlled trials to international guidelines]. 895 12

Combination therapy is a cost-effective and rational approach to treatment of severe hypertension and of mild to moderate hypertension that is refractory to monotherapy. The method has several advantages, most notably improved tolerability and enhanced antihypertensive efficacy. Long-term prospective studies are needed to confirm that such agents as calcium channel blockers, ACE inhibitors, and alpha 1 blockers reduce end-organ damage more effectively than do older antihypertensive drugs. However, scientific evidence strongly suggests that reducing risk factors for end-organ damage reduces heart, brain, kidney, and large-artery injury. Alpha 1 blockers appear to be a particularly suitable choice for use in combination regimens. The only class of agents that should be avoided in combination with alpha 1 blockers is central alpha agonists; all other agents act in an additive or synergistic fashion. Unlike diuretics and beta blockers, alpha 1 blockers do not adversely affect serum lipid, glucose, or insulin levels. In fact, alpha 1 blockers may improve these measurements and also counteract the adverse effects of other antihypertensive agents on them. Alpha1-blocker therapy may bring about regression of LVH, and it does not have deleterious effects on disorders that often coexist with hypertension (e.g., gout, chronic obstructive lung disease, peripheral ischemia).
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PMID:Alpha 1-blocker combination therapy for hypertension. 974 10

Free radicals including peroxynitrite are induced in Multiple Sclerosis (MS). Antioxidant and peroxynitrite inhibitor uric acid (UA), suppresses the MS animal model experimental autoimmune encephalomyelitis (EAE). MS patients have lower average serum UA than controls. An inverse relationship exists between MS and gout Glatiramer acetate (GA) suppresses EAE and is beneficial in relapsing MS. We investigated serum UA changes during open-label treatment of relapsing MS with GAA. Ten patients (six females, four males, aged 19 to 39 years, mean age 32 years) completed 6 months of GAA (Copaxone 20 mg s.c daily). Of these, nine completed 12 months. After 6 months on GAA, serum UA (normal, 173359 micromol/ml for women, 258-491 micromol/ml for men) increased in nine and marginally decreased (302 to 300 micromol/ml) in a single patient. Mean UA significantly increased from 240 to 303 micromol/ml (P=0.0014). At 12 months, UA remained significantly higher than at start (P=0.006) decreasing in only one patient. In contrast, we found no significant UA changes after 6 and 12 months of treatment in 21 MS patients treated with interferon beta1-a (Avonex), or in 11 treated with interferon beta1-a (Rebif), or in five placebo-treated controls. Increasing UA, a natural inhibitor of free radicals, may represent a mechanism of action of glatiramer acetate in MS.
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PMID:Increase in serum levels of uric acid, an endogenous antioxidant, under treatment with glatiramer acetate for multiple sclerosis. 1121 32

Chronic lead poisoning may cause hypertension, gout, and renal insufficiency. Most experimental poisoning studies have involved the use of high doses over short periods (ie, acute poisoning). Although chelating treatment leads to remission of acute lead nephropathy, its effects in the treatment of chronic poisoning are unclear. The aims of this study were to evaluate renal alterations produced during chronic lead poisoning and their progression when poisoning was over and to determine the efficiency of chelating treatment with calcium disodium ethylenediaminetetraacetate (EDTA). In this study, 56 male Wistar rats were administered lead in drinking water (500 ppm lead acetate) over 90 days. The control group consisted of 21 nonexposed rats. Seven rats from each group were killed on days 60 and 90. At the end of the 90-day period, 21 of the lead-exposed rats were treated with disodium monocalcium EDTA (50 mg/kg/d x 5 days) intraperitoneally, and 21 were administered serum saline by the same route. Three treatment courses were given separated by 9 days free of treatment. Seven rats from each subgroup were sacrificed at the end of each treatment course. Main findings related to poisoning were hypertrophy and vacuolization of medium and small arteries; mucoid edema and muscular hypertrophy in arterioles; loss of cell brush borders, cell loss, and intranuclear inclusion bodies in the proximal tubule; and fibrosis and the presence of infiltrates in the interstitial component. Treatment with EDTA slowed the progression of most alterations. No damage associated with the use of the chelating agent was observed. Longer term studies of the effects of this drug are required to establish whether the damage caused by lead poisoning may be reversed.
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PMID:Experimental lead nephropathy: treatment with calcium disodium ethylenediaminetetraacetate. 1208 80


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